Relationship Between Serum Hs-CRP?TNF-??IL-6 And White Mater Integrity Before And After Treatment Of Major Depressive Disorder

Objective:Inflammation and immunity regulating has always been considered may play a key role in the pathogenesis of MDD.Current evidences suggest that systemic inflammation may affect white matter(WM)integrity.To further explore the possible pathogenesis and treatment mechanism of MDD from the perspective of inflammation and immunity,our study evaluated the relationship between white matter integrity and serum cytokine levels during the first depressive episode or antidepressant-free MDD patients before and after treatment,using diffusion tensor imaging(DTI)of tract-based spatial statistics(TBSS)method.We also analyze the relationship between the microstructure change of WM and the clinical symptoms before and after treatment.Methods:According to the journal of the American Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition(Diagnostic and Statistical Manual of getting Disorders,Fifth Edition,DSM-5)MDD diagnostic criteria for acute phase into the group of patients with MDD,We also use a simplified version of the semi-structured clinical interview MINI tools to establish MDD Diagnostic.Gender,age,BMI and education level matched healthy control were recruited.All subjects were requested to finish the self-made general information collection table and evaluated by the 17-item Hamilton depression scale(HAMD),young's manic scale(YMRS)at baseline.Both MDD group and healthy control(HC)need to finish MRI scan and being collected blood samples for the quantitatively measure cytokines(hs-CRP?TNF-?and IL-6)at baseline.The MDD group accepted with monotherapy(venlafaxine)target dose of 150 ? 225 mg daily treatment for 8 weeks.After treatment,The MDD group need to finish the DTI scan and being collected blood samples again and being assessed the mood changes and therapeutic effect at the same time.Results:1?For all cytokines,there were no significant differences between the groups;After treatment the scores of 17-HAMD were significantly decreased.Serum level of hs-CRP,TNF-? and IL-6 in post-treatment MDD were significantly decreased and was lower than that in HC.2?There were no statistically significant differences in baseline serum triglycerides,total cholesterol,and low-density lipoprotein between the MDD group and the HC group.After treatment,the levels of total cholesterol and low-density lipoprotein were significantly higher than baseline,but there were no statistically significant differences between the MDD group and the HC group.3?The baseline level of TNF-? in MDD was negatively related to the course of the disease;Neither the level of hs-CRP nor IL-6 in Pre-treatment MDD showed a correlation associate with the age,BMI,age of onset,episodes of disease,duration and the sores of 17-HAMD.4?Fractional anisotropy(FA)values of the bilateral superior fronto-occipital fasciculus(SFO),posterior limb of internal capsule and fornix in pre-treatment MDD patients were decreased significantly to the HS(p < 0.05);FA values in these regions in post-treatment MDD patients have risen to normal levels except the bilateral superior fronto-occipital fasciculus,the FA values in the bilateral superior fronto-occipital fasciculus were still significantly lower than that in HC.There was no region in post-treatment MDD show higher FA value than that in HC.5?FA values of the left posterior limb of internal capsule were significantly inversely correlated with the peripheral hs-CRP levels in both pre-treatment MDD and post-treatment patients(p<0.05);6?FA values of the corpus callosum genu were significantly inversely correlated with the peripheral hs-CRP levels in pre-treatment MDD patients;No regions showed significant correlation between the FA values and other serum cytokine levels in MDD patients before and after treatment.Among the HS,no regions exhibited a significant correlation between FA values and serum cytokine levels.Conclusion:1?We speculate that the reduction in plasma hs-CRP?TNF-? and IL-6 levels in MDD patients after effective antidepressant treatment result from the pharmacologic effect of venlafaxine.These inflammatory cytokines may be associated with the treatment mechanism of MDD.2?The decreased FA values of the bilateral posterior limb of internal capsule,superior fronto-occipital fasciculus(SFO)and fornix at baseline restore to some extent after effective antidepressant treatment.Our results suggest that the integrity of WM connection in the cortical-subcortical circuit,the key structure associated with emotional processing,such as fornix and the fibers which related to emotion regulation play key roles in the pathology and treatment mechanism of MDD.3?The WM integrity might be more sensitive to hs-CRP in MDD patients than in HS,and the microstructural changes in the WM tracts might occur even in the early stage of MDD patients with normal hs-CRP level.The hs-CRP may be involved in the pathogenesis of MDD.4?The serum hs-CRP level,a marker of systemic inflammation that may reflect the neuroinflammatory state in MDD patients was associated with the change of FA value under DTI scan in the brain regions of the patients before and after treatment,thus we speculated that systemic inflammatory may be involved in the occurrence of early MDD and treatment.5? We assumed that the WM of the corpus callosum genu may be normal in the early stage of MDD or the WM alterations in this region may lag behind those in the bilateral superior fronto-occipital fasciculus(SFO),posterior limb of internal capsule and fornix.